Ravulizumab for Kidney Transplant

(AWAKE Trial)

Recruiting at 99 trial locations

Overseen By Alexion Pharmaceuticals, Inc. (Sponsor)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alexion Pharmaceuticals, Inc.

Disqualifiers: Acute kidney injury, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

450 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to demonstrate the efficacy of ravulizumab vs placebo in reducing the severity of DGF as measured by time to freedom from dialysis in adult participants who are at high risk of DGF after undergoing transplant of deceased donor kidney.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

Is Ravulizumab safe for use in humans?

Ravulizumab has been generally well tolerated in clinical trials for conditions like atypical hemolytic uremic syndrome, with common side effects including headache, diarrhea, and vomiting. No unexpected safety events were reported, and it has been used safely in both adults and children. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults at high risk of delayed graft function (DGF) after receiving a kidney transplant from a deceased donor. Specific eligibility details are not provided, but typically participants must meet certain health standards and not have conditions that could interfere with the study.

Inclusion Criteria

I am eligible for a kidney transplant from a high-risk donor.

I am eligible for a kidney transplant from a donor after circulatory death.

I am 18 years old or older.

Exclusion Criteria

My kidney donor matches specific criteria.

I have been diagnosed with severe acute kidney injury.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ravulizumab or placebo intravenously to evaluate efficacy in reducing delayed graft function

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on time to freedom from dialysis

4 weeks

Treatment Details

Interventions

• Ravulizumab

Trial Overview The study aims to test if Ravulizumab can reduce the severity of DGF compared to a placebo. It measures how long it takes patients to be free from dialysis post-transplant. Participants will be randomly assigned to receive either Ravulizumab or placebo in a double-blind manner.

Participant Groups

Group I: Ravulizumab Experimental Treatment 1 Intervention

Participants will receive an IV dose of ravulizumab.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive an IV dose of placebo.

Who Is Running the Clinical Trial?

Alexion Pharmaceuticals, Inc.

Lead Sponsor

Trials

267

Recruited

141,000+

Dr. Alberto R. Martinez

Alexion Pharmaceuticals, Inc.

Chief Medical Officer since 2010

MD from University of Sao Paulo

Marc Dunoyer

Alexion Pharmaceuticals, Inc.

Chief Executive Officer since 2021

PhD in Molecular Biology

Findings from Research

Ravulizumab is a monoclonal antibody that inhibits complement C5, effectively preventing cell lysis in conditions like paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), and received its first approval in the USA in December 2018 for treating adults with PNH.

The drug has been developed using technology to extend its half-life, allowing for less frequent dosing, and is currently being evaluated for additional uses in myasthenia gravis and IgA nephropathy, as well as a subcutaneous formulation for easier administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ravulizumab: First Global Approval. McKeage, K.[2020]

Ravulizumab is an effective treatment for atypical hemolytic uremic syndrome (aHUS), resolving thrombotic microangiopathy in 54% of adult and 78% of pediatric treatment-naïve patients within 26 weeks, making it a promising option for both groups.

With a maintenance dosage of once every 4-8 weeks, ravulizumab offers a more convenient treatment schedule compared to its predecessor eculizumab, which requires dosing every 2-3 weeks, while maintaining a good safety profile with common side effects like headache and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ravulizumab: A Review in Atypical Haemolytic Uraemic Syndrome. Syed, YY.[2022]

In a trial involving 80 kidney transplant recipients with preformed donor-specific antibodies, eculizumab significantly reduced the treatment failure rate to 8.8%, compared to an expected 40% with standard care, indicating its efficacy in preventing acute antibody-mediated rejection (AMR).

Eculizumab was well tolerated with no new safety concerns, and at 36 months, the graft and patient survival rates were 83.4% and 91.5%, respectively, suggesting it is a safe option for prophylaxis against AMR in kidney transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies. Glotz, D., Russ, G., Rostaing, L., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Ravulizumab: First Global Approval. [2020]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Ravulizumab: A Review in Atypical Haemolytic Uraemic Syndrome. [2022]

3. Denmark pubmed.ncbi.nlm.nih.gov

Upfront use of eculizumab to treat early acute antibody-mediated rejection after kidney allotransplantation and relevance for xenotransplantation. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies. [2023]